New prostate drug shrinks tumours, B.C. scientists say

Tuesday, June 15, 2010

By Pamela Fayerman, Vancouver Sun

June 14, 2010 - Regression of Castrate-Recurrent Prostate Cancer. On day 25 of the B.C. Cancer Agency experiment, prostate tumours were removed from animals. The five large tumours, on left, were treated with a placebo; the five small tumours, on right, were treated with the new drug that caused them to shrink substantially.

Photographed by:Handout, B.C. Cancer Agency

VANCOUVER — B.C. scientists have developed an experimental new drug to shrink prostate cancer tumours, based on molecules extracted from a marine sponge collected in New Guinea.

Their study, published Monday in the journal Cancer Cell, shows the experimental drug — EPI-001 — not only shrunk tumours but did so without apparent toxic effects on the cancer-afflicted laboratory mice who got injections of the drug.

"The day I saw the way tumours were actually shrinking I ran all around the building showing everyone the pictures," said Marianne Sadar, a scientist with the BC Cancer Agency. Sadar has spent many years looking for new drugs to help men who suffer relapses when their cancer becomes resistant to what's called androgen ablation therapy: surgical or drug treatment meant to stop production of male hormones (testosterone) that fuel tumour growth.

In such men, prostate cancer begins to grow again and standard therapies may increase survival by only about two months, according to the new study.

Several years ago, Sadar teamed with Raymond Andersen, a natural compounds chemist and University of B.C. professor, who has spent much of his career combing the seas for natural compounds to be used as anti-cancer medicines.

Sadar said there have been a number of chemotherapy drugs developed from sponges. And a survey by the U.S. National Cancer Institute showed that natural products or synthetic versions of natural products make up about 64 per cent of anti-cancer compounds currently in pre-clinical studies or clinical trials. More than 70 per cent of the Earth's surface is covered by oceans and it's been estimated there are more than 100,000 species of invertebrates in the oceans. Sponges are considered ideal for providing raw materials for the development of new drugs.

But in a rather surprising turn of events, scientists discovered that the compounds in the marine sponge had a chemical composition resembling a compound called BADGE (Bisphenol A Diglycidic Ether) which indicated that the sponge was harvested from contaminated water possibly polluted by ship traffic. Sadar said the sponge material was collected from a shipping route and it would appear the sponge "bio-accumulated the metabolites or byproducts of bisphenol A," a ubiquitous compound used in the plastics industry, among many others.

Bisphenol A — or BPA — is the subject of much scrutiny and concern as research has shown it can be an endocrine system disrupter and may be especially harmful to infants and children.

Sadar said she and her team of scientists isolated and extracted only the sponge's desired compound — EPI-001 — into a purified form and then synthesized it. The drug does not contain BPA and indeed, in the study, mice getting high doses of EPI-001 suffered no ill-effects on their internal organs as shown by pathologic examination. Furthermore, future studies must satisfy Food and Drug Administration guidelines before being used in humans in clinical trials.

Sadar said researchers hope to set up a cancer agency spinoff company, garner venture capital and perhaps partner with a pharmaceutical company to enter the next phase of research — trials in humans.

In a commentary in the journal, the research by Sadar and her 13 co-authors is praised by Dr. Timothy C. Thompson, of the University of Texas M.D. Anderson Cancer Centre: "It is a rare occasion in prostate cancer research when such a unique and promising therapeutic agent for advanced prostate cancer is developed."